This is an application for an R01 grant entitled, "Novel DT-MRI Analyses of White Matter in Schizophrenia". The goal of this five-year award is to apply new approaches for evaluating white matter abnormalities in schizophrenia using Diffusion Tensor Magnetic Resonance Imaging (DT-MRI) and DT-MRI post-processing techniques. This work builds upon our previous work showing that white matter tracts can be detected and delineated with DT-MRI. These tools will be further developed and then applied to DT-MRI data in order to evaluate white matter fiber tract abnormalities in schizophrenia (i.e., uncinate fasciculus, corpus callosum and cingulum bundle). The specific aims of this project are: (1) to developed and apply novel spatial normalization and registration methods;(2) to develop and apply a novel 3D DT-MRI tractography method based on stochastic modeling, (3) to develop and apply automated tools for grouping tractography results into anatomically meaningful white matter bundles and ROIs, and (4) to evaluate fiber tract integrity in a patient population by a lying new quantitative measures of diffusion in white matter, and comparing their mean values in the aforementioned arcellated ROIs. Although the clinical focus of this grant is on schizophrenia, this technology will be directly applicable to other fields using data from DTI, such as for the early detection of white matter damage in the developing infant brain, exploration and characterization of white matter disruptions caused by MS lesions, and visualization of important white matter tracts during neurosurgical procedures. Of further importance, we plan to make these tools available to other researchers by implementing them in an open-source platform. We believe that these latter goals are particularly important for disseminating novel techniques for analyzing DT-MRI data to the larger neuroscience community.